身体全体のミトコンドリアの糖のエネルギー代謝こそ、生命活動を支える根本であり、最重要であるということを述べてきました。逆に言えば、そのミトコンドリアの機能が障害されるようなことがあると、身体の機能は衰えていくということになります。
それでは、ミトコンドリアはどのような要因で障害されるのでしょうか？？
ミトコンドリアの機能異常は、単一の原因で生じるものではなく、複数の要因が重なり合うことで引き起こされますが、主に「外的要因」と「内的要因」に分けられます。
「外的要因」としては、以下のようなものがあります▽
・化学物質（農薬・重金属など）[188-192]
・大気汚染[191,193-196]
・紫外線[197-200]
・電磁波（非電離放射線）[201-204]
・ウイルス感染[205-210]
「内的要因」としては以下のようなものがあります▽
・慢性炎症[211-214]
・腸内環境異常（dysbiosisやLPSなど）[215-217]
・精神的・肉体的ストレス、自律神経/ホルモンバランス異常[218-220]
・酸化ストレス（PUFAによる脂質過酸化など）[221-225]
・栄養状態悪化（ミネラル不足など）[225-228]
この中で当院が大きな問題だと思っているのは、多価不飽和脂肪酸（Polyunsaturated Fatty Acids：PUFA）によるミトコンドリア障害です。PUFAがもたらす害についての詳細は第四章に譲りますが、PUFAは酸化されやすく、活性酸素（ROS）によって脂質過酸化反応を起こしやすい性質があります[229-232]。その結果、反応性の高い有害なアルデヒド（4-HNEなど）が生成されると、ミトコンドリアの電子伝達系やATP合成酵素を障害します[233-235]。また、内膜の主要脂質であるカルジオリピンが過酸化されると膜構造が不安定化し、エネルギー産生効率の低下やシトクロムcの放出を招き、炎症や細胞死の引き金となります[236-238]。さらに、遊離PUFA自体も脱共役や呼吸阻害を引き起こし、ミトコンドリア機能を低下させる要因となり得ることがわかっています[239,240]。
また、慢性炎症もミトコンドリア機能に深く関与しています。炎症性サイトカインやLPS（リポポリサッカライド：腸内細菌の菌体内毒素）は、ミトコンドリアの代謝経路を変化させ、解糖系への偏位（いわゆる代謝リプログラミング＝免疫代謝）を引き起こします[241-243]。この状態が持続すると、ミトコンドリアの機能は徐々に低下し、細胞はエネルギー効率の低い状態に固定され、病的な状態に陥ってしまいます。
さらに、外的要因では、環境中の化学物質や重金属、電磁波、精神的ストレスなども、ミトコンドリアに対する慢性的な負荷として働きます。これらの要因のうち、特にある種の化学物質や重金属で、ミトコンドリアの品質管理機構（ミトファジー）が障害され、損傷したミトコンドリアの蓄積を招くことが知られています[244-248]。
このように、複数の要因で引き起こされるミトコンドリア機能異常は、細胞レベルのエネルギー代謝の恒常性の破綻が全身に波及した状態であり、身体全体の状態を反映した現象といえます。そして、近年では、ミトコンドリアは単なるエネルギー産生装置ではなく、免疫応答や炎症シグナル、さらには遺伝子発現の制御にも関与する統合的な制御システムとして機能していることが明らかになってきています。このように、ミトコンドリアは外的・内的要因によって常にさまざまな「負荷」を受けているのです。
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